Genes suggest schizophrenia risk leads to cannabis use more strongly than cannabis leads to schizophrenia
A two-sample Mendelian randomisation study found some evidence that trying cannabis raises schizophrenia risk, with a small effect, and stronger evidence that genetic risk for schizophrenia makes cannabis use more likely.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Weak genetic instruments for cannabis and an ever-used measure that cannot see dose; the authors say their cannabis estimate is probably conservative. A 2018 MR study found a larger causal effect.
A genetic test of which way the cannabis and psychosis link runs, and why the answer is "both, unevenly".
Significant findings
Gage and colleagues used Mendelian randomisation: gene variants tied to a trait stand in for the trait, which avoids some confounding. They used published genome-wide data on cannabis initiation (the International Cannabis Consortium) and schizophrenia (the Psychiatric Genomics Consortium), and tested both directions.
Cannabis to schizophrenia: "some evidence consistent with a causal effect" (odds ratio 1.04 per doubling of the odds of cannabis initiation; 95% CI 1.01 to 1.07). Schizophrenia to cannabis: "strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation" (OR 1.10; 1.05 to 1.14). They conclude cannabis may raise risk "although the size of the causal estimate is small", and that "schizophrenia risk predicts cannabis initiation".
The other direction
The authors give reasons their cannabis estimate may be too low. The cannabis gene variants were weak predictors; none reached genome-wide significance. The cannabis measure was "Have you ever used cannabis?", with "no distinction between having tried cannabis once and having used it every day for many years". They write that if the link is causal, "exposure intensity would be the relevant risk factor", and that ever-use is linked to psychosis much more weakly than heavy use. They also note the stronger reverse result may be "possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation". A 2018 Mendelian randomisation study (Vaucher, Molecular Psychiatry) found a larger causal estimate; it is in this library.
So this does not refute the dose-response meta-analysis (Marconi 2016). It says part of the observed link may run the other way, and it could not test dose at all.
Funding
UK Medical Research Council and other public funders. The authors declare no conflicts.
What this does not show
It does not measure heavy use, high-potency cannabis or age at first use. Nothing here says anyone should start or stop using cannabis or any medication.
Worth asking
If psychosis runs in my family, what is known about heavy or high-potency cannabis use for someone like me?
Source
Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study — Gage SH, Jones HJ, Burgess S, Bowden J, Davey Smith G, Zammit S, Munafo MR (2017)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1017/S0033291716003172
DOI: 10.1017/S0033291716003172
How this was scored
- Study design
- Case-control study
- Funding
- Independently funded
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published October 2, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 59 out of 100 on our published rubric. One caveat travels with that badge: Weak genetic instruments for cannabis and an ever-used measure that cannot see dose; the authors say their cannabis estimate is probably conservative. A 2018 MR study found a larger causal effect. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study — Gage SH, Jones HJ, Burgess S, Bowden J, Davey Smith G, Zammit S, Munafo MR (2017). Published in: Reputable peer-reviewed journal. DOI: 10.1017/S0033291716003172. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Case-control study. Funding: Independently funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.